The role of T cell help in the production of antibodies specific for Galα1–3Gal

N Cretin, J Bracy, K Hanson… - The Journal of Immunology, 2002 - journals.aai.org
N Cretin, J Bracy, K Hanson, J Iacomini
The Journal of Immunology, 2002journals.aai.org
The majority of xenoreactive natural Abs in humans recognize the carbohydrate Ag present
on pig tissue, Galα1–3Galβ1–4GlcNAc-R (αGal), synthesized by the enzyme UDP
galactose: β-d-galactosyl-1, 4-N-acetyl-d-glucosaminide α (1–3) galactosyltransferase or
αGT. Using αGT knockout mice (GT 0 mice), which like humans produce serum Abs that bind
αGal, we examined the role of T cells in production of Abs specific for αGal. GT 0 mice were
crossed with TCR-β knockout mice (TCR-β 0) to generate double-knockout mice (GT 0/TCR …
Abstract
The majority of xenoreactive natural Abs in humans recognize the carbohydrate Ag present on pig tissue, Galα1–3Galβ1–4GlcNAc-R (αGal), synthesized by the enzyme UDP galactose: β-d-galactosyl-1, 4-N-acetyl-d-glucosaminide α (1–3) galactosyltransferase or αGT. Using αGT knockout mice (GT 0 mice), which like humans produce serum Abs that bind αGal, we examined the role of T cells in production of Abs specific for αGal. GT 0 mice were crossed with TCR-β knockout mice (TCR-β 0) to generate double-knockout mice (GT 0/TCR-β 0). While GT 0/TCR-β+ mice exhibited an age-dependent increase in the serum titer of natural Abs specific for αGal, a similar increase was not observed in GT 0/TCR-β 0 mice, and the titer of αGal-specific Abs in double knockouts was significantly lower than in age-matched GT 0/TCR-β+ mice. Immunization with pig cells resulted in a significant increase in the serum titer of αGal-specific Abs in GT 0/TCR-β+ mice, but had no effect on the level of αGal-specific serum Abs in GT 0/TCR-β 0 mice. Treatment of GT 0/TCR-β+ mice with anti-CD40L Abs before immunization with pig cells prevented sensitization to αGal. Our data suggest that the majority of αGal-specific Abs are T cell dependent and that production of αGal-specific Abs after sensitization can be prevented by blocking costimulatory pathways.
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